OBJECTIVES:

Increasing use of single-arm trials (SATs) has been driven, in part, by targeted therapies for niche hemato-oncological indications. However, acceptance of SAT-based Health Technology Assessment (HTA) submissions with or without external comparators (ECs) is still uncertain. The aim of this research is to provide insights and trends in the use of SATs in EMA and HTA submissions, and the use and acceptability of different EC methods in HTA submissions.

METHODS:

Indications for drug uses approved by EMA between January 2018 and April 2022 hemato-oncology were identified. Consequently, HTA reports based solely on SAT-data of corresponding drugs from NICE (England), G-BA (Germany), HAS (France), TLV (Sweden) and ZIN (the Netherlands) were investigated. Appropriateness of ECs was determined by assessing payers’ criticism in the appraisal and inclusion or exclusion in the decision justification.

RESULTS:

51 EMA approvals in hemato-oncology were identified, of which 29% (15 indications, for 11 different drugs) were based exclusively on SAT-data. Regulatory approvals based on SATs were more common in later years: 27% (6/22) in 2018-2019 versus 31% (9/29) in 2020-2022.

For these 15 indications, 48 HTA submissions with SAT-data as main type of evidence were identified. In 88% (42/48) of submissions, an EC was provided. In 83% (35/42) of submissions with an EC, at least one of the ECs had a real-world evidence (RWE) component. 57% (24/42) of ECs were found inappropriate/unusable for decision-making, 19% (8/42) of ECs were found acceptable and were used to inform the decision and 24% (10/42) of ECs were considered uncertain and/or it was unclear if they were used in the recommendation.

CONCLUSIONS:

There is an increasing proportion of SAT designs within submissions accepted by EMA, resulting in many SAT-based HTA submissions. While ECs are frequently provided in these, their acceptability by HTA bodies is still mixed.